The Powder Room - Improving Drug Water Solubility

Laboratoria Smeets

In collaboration with Ghent University, Laboratoria Smeets has developed a new granulating technology capable of significantly improving drug water solubility. Managing director Dr Jef Verplaetse explores its impact on bioavailability, and the advantages of operating twin-screw hot-melt extruders at lower temperatures.

Improving Powder Solubility

Could you introduce yourself and give us an outline of your company strategy?

Dr Jef Verplaetse: Founded in 1973, Laboratoria Smeets is a privately owned Belgian company focusing on the production of pharmaceutical powders, which we blend and then package for the end user. We're based in Antwerp, Belgium, where we have three plants. In addition to developing powders, we are involved in improving solubility and the treatment of chronic inflammation. In collaboration with Ghent University, we have developed a technique for converting drugs with poor water solubility (such as class II or class IV of the Biopharmaceutics Classification System) into highly soluble granules.

Why did you develop this technique?

Most of the newly developed molecules for pharmaceutical applications have problems when it comes to water solubility. This is a major issue. If a molecule is not water soluble, it is highly unlikely to be very active and will probably lack bioavailability. It will simply pass through the body and have no effect. So in order to enhance drug efficacy, we need to develop a technology to improve water solubility. That is what our technology does.

How does it work?

The idea of using twin-screw extruders for the granulation of drug preparations goes back to the 1980s. However, the granules produced back then were not homogenous, and required a great deal of optimisation. Recent developments focusing on improving the screw profile, as well as the materials used, have meant that twin-screw extruders can now be used for producing homogenous granules for drug preparation. Laboratoria Smeets uses a twin-screw granulator (Pharma TSG 24) supplied by Thermo Scientific. This technology allows for extremely intense and effective blending under strictly controllable conditions, helping ensure API stability.

Twin-Screw Hot-Melt Technology

What separates your granulation technique from those of competitors?

We're using something called twin-screw hot-melt technology. Usually, this is associated with relatively high melting temperatures, around 150-200°C. For some APIs, this is acceptable. But for others, it's a problem, because you start to see degradation. Also, if you melt something at 150-200°C, you get a hard material - like plastic - from your extruder. You then have to grind it in order to make it usable. But we have developed a technology that works at 50°C. So it's a much lower, more normal sort of temperature, which most of the APIs can stand. It also means we get a very soft powder directly out of the extruder. From there, we can put it straight into the consumer packaging and it's ready to use - we don't have to treat it with anything afterwards. It's a very simple, straightforward, one-step process.

So what effect does your technology have on drug efficacy?

Our technique significantly improves the rate and, to a lesser degree, the extent of dissolution. This means the API is more quickly released, often increasing bioavailability and thereby boosting efficacy. It also dramatically reduces wastage, as less API is needed to create the same clinical effect. We have also managed to develop techniques that facilitate supersaturation, allowing us to exceed natural dissolution for the API.

What markets are you currently targeting?

At the moment, we're focusing on the veterinary sector. However, the reasons for using our technology here stretch beyond just improving bioavailability - there are also some more practical issues. While mixing drugs with animal feed is simpler than dissolving them in water, it's difficult to control the concentration level in feed granules, or accurately estimate batch sizes. Also, sick animals tend not to eat, and they certainly won't swallow tablets. However, they will drink. Highly soluble drugs are therefore in great demand.

Do you plan to branch out into the human drugs market?

The main reason we're not involved with humans at the moment is to do with our marketing strategy. However, the technology is ready for it, and we are certainly interested in trying. Bioavailability is going to become ever-more important for human medicines. Improving it also means a drug's effect, as a function of a given dose, can be better understood.

Where do you see this technology being used in the future?

The area that could be really interesting is generics. Once a drug becomes generic, there's not much value in it any more. But if you can use our technique to improve its effectiveness, this translates into a higher price - as well as being better for the patient. What's more, our technology is patented, so you also add a new time frame of protection.

Do you have any interesting projects in the pipeline?

We have developed a technology for cocrystallisation. It's looking extremely promising for APIs.